HIV Viral Reservoirs and Monocyte Activation in HIV-Associated Atherosclerosis

简介(申请人提供)：许博士是世界上少数在艾滋病毒方面拥有广泛研究和临床专业知识的心脏病专家之一，在过去的十年里一直致力于艾滋病毒背景下的心血管疾病的研究。她职业生涯的最初阶段是：1)在旧金山总医院(SFGH)建立HIV心脏科诊所；2)在旧金山总医院心脏科开发基础设施以进行POR研究，其中包括开发用于临床研究的血管实验室；以及3)开展评估HIV感染和心血管疾病(CVD)机制的研究。她的研究结果表明，1)艾滋病毒感染与心血管疾病独立相关，与传统风险因素或艾滋病毒药物无关，2)有效治疗艾滋病毒感染背景下的慢性炎症是心血管风险增加的基础，3)确定减少艾滋病毒相关炎症和心血管风险的治疗方法。在她的5年K24奖项提案中，她计划增加在艾滋病毒感染、艾滋病毒相关炎症和心血管疾病领域指导初级调查人员的时间，以帮助他们在未来成为成功的独立研究人员。她的K24提案将扩展她目前由R01资助的研究，通过研究HIV感染治疗背景下HIV相关动脉粥样硬化的潜在机制，实现以下两个具体目标：1)通过颈动脉内中膜厚度(IMT)评估单核/巨噬细胞激活在动脉粥样硬化进展中的作用，通过血流介导的肱动脉血管扩张(FMD)评估内皮功能障碍，以及有效治疗HIV感染者中的微血管疾病(通过充血峰值速度测量)2)以确定在有效治疗HIV感染者中单核/巨噬细胞激活在动脉粥样硬化进展、内皮功能和微血管疾病中的作用。K24提案将提供受试者访问、血管成像以及临床和实验室数据，以支持在艾滋病毒相关心血管疾病领域以患者为导向的转化性研究中指导新的研究人员。

DESCRIPTION (provided by applicant): Dr. Hsue is one of the few cardiologists in the world with both extensive research and clinical expertise in HIV and has devoted the last ten years studying cardiovascular disease in the setting of HIV. The initial part of her career was spent 1) establishing a HIV Cardiology Clinic at San Francisco General Hospital (SFGH), 2) developing the infrastructure to perform POR research in the Cardiology Division at SFGH which has included development of a vascular laboratory for clinical research, and 3) performing studies that evaluate the mechanisms underlying HIV infection and cardiovascular disease (CVD). The findings from her work have shown that 1) HIV infection is independently associated with CVD, independent of traditional risk factors or HIV medication, and 2) chronic inflammation in the setting of effectively treated HIV infection underlies this increased CV risk, and 3) identifying therapies to reduce HIV-associated inflammation and CV risk. For her 5 year K24 award proposal, she plans to increase her time spent mentoring junior investigators in the fields of HIV infection, HIV-associated inflammation, and cardiovascular disease for the purpose of helping them to become successful independent researchers in the future. Her K24 proposal will extend upon her current R01 funded investigations by studying the underlying mechanism of HIV-associated atherosclerosis in the setting of treated HIV infection with the following two Specific Aims: 1) To characterize the role of monocyte/macrophage activation in atherosclerotic progression as assessed by carotid artery intima-media thickness (IMT), endothelial dysfunction as assessed by flow-mediated vasodilation of the brachial artery (FMD), and microvascular disease (measured by peak hyperemic velocity) in effectively treated HIV-infected individuals 2) To determine the role of HIV reservoir on atherosclerotic progression, endothelial function, and microvascular disease in effectively treated HIV-infected individuals. The K24 proposal will provide subject visits, vascular imaging, and clinical and laboratory data to support mentoring new investigators in patient-oriented translational research in the field of HIV-related cardiovascular disease.